Utility and limitations of patient-adjusted D-dimer cut-off levels for diagnosis of venous thromboembolism - A systematic review and meta-analysis.

Gerber, Joël L; Messmer, Anna S; Krebs, Tobias; Müller, Martin; Hofer, Debora M; Pfortmueller, Carmen A (2023). Utility and limitations of patient-adjusted D-dimer cut-off levels for diagnosis of venous thromboembolism - A systematic review and meta-analysis. Journal of internal medicine, 294(1), pp. 110-120. Wiley 10.1111/joim.13650

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PURPOSE

To systematically assess test performance of patient-adapted D-dimer cut-offs for the diagnosis of venous thromboembolism (VTE).

METHODS

Systematic review and analysis of articles published in PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. Investigations assessing patient-adjusted D-dimer thresholds for the exclusion of VTE were included. A hierarchical summary receiver operating characteristic model was used to assess diagnostic accuracy. Risk of bias was assessed by QUADAS-2.

RESULTS

68 studies involving 141,880 patients met the inclusion criteria. The standard cut-off revealed a sensitivity of 0.99 (95% confidence interval [CI] 0.98 - 0.99) and specificity of 0.23 (95% CI 0.16 - 0.31). Sensitivity was comparable to the standard cut-off for age-adjustment (0.97 [95% CI 0.96 - 0.98]) and YEARS algorithm (0.98 [95% CI 0.91 - 1.00]) but lower for pre-test probability (PTP)-adjusted (0.95 [95% CI 0.89 - 0.98) and COVID-19-adapted thresholds (0.93 [95% CI 0.82 - 0.98]). Specificity was significantly higher across all adjustment strategies (age: 0.43 [95% CI 0.36 - 0.50]; PTP: 0.63 [95% CI 0.51 - 0.73]; YEARS algorithm: 0.65 [95% CI 0.39 - 0.84]; and COVID-19: 0.51 [95% CI0.40 - 0.63]). The YEARS algorithm provided the best negative likelihood ratio (0.03 [95% CI 0.01 - 0.15]), followed by age-adjusted (both 0.07 [95% CI 0.05 - 0.09]), PTP (0.08 [95% CI 0.04 - 0.17), and COVID-19-adjusted thresholds (0.13 [95% CI 0.05 - 0.32]).

CONCLUSIONS

This study indicates that adjustment of D-dimer thresholds to patient-specific factors is safe and embodies considerable potential for reduction of imaging. However, robustness, safety, and efficiency vary considerably between different adjustment strategies with a high degree of heterogeneity. This article is protected by copyright. All rights reserved.

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